Predictors of CVD among breast cancer survivors in an integrated health system

项目总结/摘要 乳腺癌幸存者在以下情况下发生和死于心血管疾病（CVD）的风险很高 乳腺癌诊断，但风险增加的亚群和干预目标尚未得到很好的- 表征了越来越多的文献将CVD与特定的心脏毒性癌症治疗联系起来。cvd风险 在乳腺癌幸存者中， CVD危险因素。然而，大多数关于乳腺癌患者人群心血管疾病风险的研究 有明显的局限性，包括CVD结局特征不佳，缺乏CVD药物依从性 数据和风险因素，以及匹配不佳的无癌对照组。需要精心设计的研究， 确定CVD事件高风险的乳腺癌幸存者亚群和 干预，同时考虑接受的特定乳腺癌治疗，CVD药物和CVD风险 因素我们建议在正在进行的乳腺癌幸存者研究中进行一项辅助研究， 克服了以往研究的局限性。这项研究将全面检查临床和行为 乳腺癌幸存者中CVD结局的预测因子，并将最大限度地利用独特的患者和数据 在Kaiser Permanente北方加州（KPNC）可用的资源。我们将比较CVD事件在 路径研究，一项年龄≥ 21岁诊断为浸润性乳腺癌的女性KPNC成员队列 （n = 4，453，R01CA 105274）在新的年龄、人种/种族、合并症史和病程中发生CVD事件 KPNC成员匹配的健康KPNC女性成员队列（n = 22，265）。具体目标是：目标1） 检查CVD事件（缺血性心脏病、卒中/一过性）的绝对风险和相对风险 缺血性发作和心肌病/心力衰竭等）和新发CVD危险因素（高血压， 糖尿病、血脂异常）的乳腺癌女性（Pathways）和无癌对照组（KPNC 匹配队列）;目的2）在有乳腺癌病史的女性中（路径），检查 按心脏毒性乳腺癌治疗类型列出的新发CVD事件和新发CVD风险因素 接受的治疗，包括化疗/生物治疗（蒽环类、曲妥珠单抗）、激素治疗 （他莫昔芬，芳香酶抑制剂）和放射治疗，控制与基线CVD相关的混杂因素 药物依从性、临床和行为风险因素、医疗保健和卫生保健系统因素，以及 社会经济地位（SES）;目的3）评估有以下病史的女性对CVD药物的依从性： 乳腺癌（Pathways）使用14年的随访数据，并检查依从性与 CVD事件的风险，控制接受的心脏毒性癌症治疗，基线CVD临床和行为 风险因素、医疗保健和卫生保健系统因素以及SES。影响：本研究的结果将 对确定CVD高风险乳腺癌亚组和确定潜在的 干预目标，如药物依从性和CVD风险因素的控制。

PROJECT SUMMARY / ABSTRACT Breast cancer survivors are at high risk of developing and dying from cardiovascular disease (CVD) following breast cancer diagnosis, but subpopulations at increased risk and targets for intervention have not been well- characterized. A growing body of literature links CVD with specific cardiotoxic cancer treatments. CVD risk among breast cancer survivors might vary by concomitant non-adherence to CVD medications and presence of CVD risk factors. However, most of the studies on CVD risk among breast cancer patient populations have had significant limitations, including poorly characterized CVD outcomes, lack of CVD medication adherence data and risk factors, and poorly matched cancer-free control groups. Well-designed studies are needed to identify subpopulations of breast cancer survivors at high risk for CVD events and modifiable targets for intervention while accounting for specific breast cancer treatments received, CVD medications, and CVD risk factors. We propose to conduct an ancillary study within an ongoing study of breast cancer survivors which will overcome limitations of prior studies. The proposed study will comprehensively examine clinical and behavioral predictors of CVD outcomes among breast cancer survivors, and will maximize unique patient and data resources available at Kaiser Permanente Northern California (KPNC). We will compare CVD events in the Pathways Study, a cohort of female KPNC members age ≥21 years diagnosed with invasive breast cancer (n=4,453, R01CA105274) with CVD events in a new age, race/ethnicity, history of comorbidity, and length of KPNC membership matched cohort of healthy KPNC female members (n=22,265). Specific aims are: Aim 1) To examine the absolute risk and relative risk of incident CVD events (ischemic heart disease, stroke/transient ischemic attack, and cardiomyopathy/heart failure, and others) and new onset CVD risk factors (hypertension, diabetes, dyslipidemia) in women with breast cancer (Pathways) and a cancer-free comparison group (KPNC matched cohort); Aim 2) In women with a history of breast cancer (Pathways), to examine the relative risk of incident CVD events and new onset of CVD risk factors, by type of cardiotoxic breast cancer treatment received, including chemotherapy/biologic therapy (anthracyclines, trastuzamab), hormonal therapy (Tamoxifen, aromatase inhibitors), and radiation therapy, controlling for confounders related to baseline CVD medication adherence, clinical and behavioral risk factors, medical care and health care system factors, and socioeconomic status (SES); Aim 3) To assess adherence to CVD medications in women with a history of breast cancer (Pathways) using 14 years of follow-up data, and to examine the association of adherence with risk of CVD events controlling for cardiotoxic cancer treatment received, baseline CVD clinical and behavioral risk factors, medical care and health care system factors, and SES. Impact: Results from this study will have important implications for identifying breast cancer subgroups at high risk of CVD and identifying potential targets for intervention, such as medication adherence and control of CVD risk factors.